It is the purpose of this project to study the mode of action and the pharmacology of antitumor agents of the ansa macrolide class. Attention is presently focused on the plant product maytansine and its naturally occurring and semisynthetic derivatives. Maytansine was found to produce metaphase arrest in a manner similar to that seen with the Vinca alkaloids, and to impair microtubule formation in L1210 cells in culture. Topics of current interest are a) a comparison of the tubulin binding properties of maytansine with those of its structural analogs; b) bioassay methods for maytansine; and c) direct comparative studies of maytansine and vincristine with reference to cell uptake, cell kill, mitotic arrest, and physiological distribution.